Radiation therapy for breast cancer has considerably changed over the years, from simple simulator-based 2-dimensional techniques to sophisticated image-guided individualized treatments, with maximally protected normal structures. This has led to a substantial improvement in the outcome of breast cancer patients in terms of disease control, survival, and quality of life. This progress is based on clinical research and paralleled by progress in delivering sophisticated radiation treatment. Clinical trials resulted in identifying patients groups who will benefit from radiation treatment. They also stimulated the development of quality assurance tools and guidelines, which are now applied in daily clinical practice. The new technical opportunities to optimize dose distributions in patients require dedicated quality assurance measures because they may be more sensitive to variations throughout the treatment. Still, a large source of variation and uncertainty in radiation therapy remains in the definition of target volumes, which is clinically significant in terms of dosimetric target coverage as well as exposure of healthy tissues. This striving for continuous improvement of patient selection and treatment will lead to further improvement of local control while at the same time improving functional and cosmetic outcome and avoiding severe late complications, including cardiac toxicity.